Endocrine Abstracts

Introduction: Short stature is a common manifestation of Noonan Syndrome (NS) that affects up to 70% of patients with this syndrome. We present 2 observations of NS associated with growth hormone (GH) deficiency.

Observations: Case 1: A 7-year-old female patient was admitted for a growth delay (height at −4 SD and weight at -1 SD). On examination, she had a dysmorphic syndrome suggestive of NS: triangular face, hypertelorism, low-implanted ears, a webbed neck, an enlarged thorax, and small hands with deep palmar folds. The ophthalmological examination was without abnormalities. Cardiac ultrasound was normal. The karyotype returned normal. The causal mutation has not been identified. Dynamic tests confirmed a partial GH deficiency. Pituitary MRI was normal. The patient was put on GH replacement therapy at the age of 8 years with a dose of 0.04 mg/kg/day with an improved velocity growth and a gain of +1 SD in height after 2 years of treatment. The dose was increased to 0.05 mg/kg/day. She has not yet started puberty. Case 2: A 5-year-old female patient was admitted for a stature delay (height at −3 SD and weight at −2 SD). On examination, she had a dysmorphic syndrome suggestive of NS: a triangular face with curly hair, hypertelorism and low implanted ears. The ophthalmological examination was without abnormalities. Cardiac ultrasound was normal. The karyotype returned normal. The causal mutation has not been identified. Dynamic tests confirmed a complete GH deficiency. Pituitary MRI was normal. The patient was put on GH replacement therapy at the age of 6 years with the dose of 0.045 mg/kg/day with improvement of velocity growth and a gain of +2 SD in height after 2 years of treatment.

Discussion: Possible mechanisms of short stature in NS include GH deficiency, neurosecretory dysfunction, and GH resistance. The PTPN11 mutation had IGF-1 levels similar to those without the PTPN11 mutation, as was the case for our 2 patients who had a normal karyotype. Early initiation and long-term GH treatment were associated with improvement in final height, whereas sex, GH dose and clinical severity did not show a significant association with final height. The delayed initiation of treatment could therefore explain the poor outcome of treatment in the first patient.